QT PRODACT: Sensitivity and Specificity of the Canine Telemetry Assay for Detecting Drug-Induced QT Interval Prolongation
The purpose of this investigation was to define the sensitivity and specificity of the canine telemetry assay for detecting drug-induced QT interval prolongation. Data from twelve studies generated in the QT PRODACT project were used in this investigation. The study design was a 4 × 4 Latin square c...
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doaj-b2895fd8ee014c4f9860c2373810a7032020-11-25T02:15:02ZengElsevierJournal of Pharmacological Sciences1347-86132005-01-01995523529QT PRODACT: Sensitivity and Specificity of the Canine Telemetry Assay for Detecting Drug-Induced QT Interval ProlongationHiroyasu Miyazaki0Hiroyuki Watanabe1Tetsuya Kitayama2Masahiro Nishida3Yasuhiro Nishi4Koji Sekiya5Hideki Suganami6Keiji Yamamoto7Japan Pharmaceutical Manufacturers Association (JPMA)/QT PRODACT, Tokyo 103-0023, Japan; Tsukuba Safety Assessment Laboratories, Banyu Pharmaceutical Co., Ltd., Ibaraki 300-2611, Japan; Corresponding author (affiliation #2). FAX: +81-29-877-2320 E-mail: Hiroyasu_Miyazaki@merck.comJapan Pharmaceutical Manufacturers Association (JPMA)/QT PRODACT, Tokyo 103-0023, Japan; Biostatistics, Banyu Pharmaceutical Co., Ltd., Tokyo 103-0026, JapanJapan Pharmaceutical Manufacturers Association (JPMA)/QT PRODACT, Tokyo 103-0023, Japan; Toxicological Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka 411-8731, JapanJapan Pharmaceutical Manufacturers Association (JPMA)/QT PRODACT, Tokyo 103-0023, Japan; Tsukuba Safety Assessment Laboratories, Banyu Pharmaceutical Co., Ltd., Ibaraki 300-2611, JapanJapan Pharmaceutical Manufacturers Association (JPMA)/QT PRODACT, Tokyo 103-0023, Japan; Tsukuba Safety Assessment Laboratories, Banyu Pharmaceutical Co., Ltd., Ibaraki 300-2611, JapanJapan Pharmaceutical Manufacturers Association (JPMA)/QT PRODACT, Tokyo 103-0023, Japan; Pharmacology & Toxicology Department, Ina Research, Inc., Nagano 399-4501, JapanJapan Pharmaceutical Manufacturers Association (JPMA)/QT PRODACT, Tokyo 103-0023, Japan; Data Management & Biostatistics, Kowa Co., Ltd., Tokyo 103-8433, JapanJapan Pharmaceutical Manufacturers Association (JPMA)/QT PRODACT, Tokyo 103-0023, Japan; Development Research Center, Takeda Pharmaceutical Co., Ltd., Osaka 532-8686, JapanThe purpose of this investigation was to define the sensitivity and specificity of the canine telemetry assay for detecting drug-induced QT interval prolongation. Data from twelve studies generated in the QT PRODACT project were used in this investigation. The study design was a 4 × 4 Latin square cross-over design and included the following drugs: MK-499, E-4031, terfenadine, haloperidol, cisapride, bepridil, propranolol, diphenhydramine, captopril, verapamil, amoxicillin, and ciprofloxacin. The estimated root squared error of the model, which estimated the slope of the QT-RR relationships for each animal, for all dogs during the pre-dosing period was 5.45%. Using the QT-RR model, the sensitivity and specificity in each cutoff value that judges QT prolongation were estimated based on the experiment errors and measurement errors in the 12 studies. When the cutoff value was 5%, the sensitivity in 10% prolongation was 0.978 and the specificity in 0% was 0.996. In conclusion, it was judged that a 5% cutoff value for changes in heart rate corrected QT interval using the canine telemetry assay is practical, and the sensitivity and specificity of the telemetry assay are very high when using the analytical method presented here. Based upon this information, the canine telemetry assay using the individual subject heart rate correction model is recommended as a sensitive test system for the in vivo assessment of risk for QT interval prolongation. Keywords:: dog, sensitivity, telemetry, QT, QTchttp://www.sciencedirect.com/science/article/pii/S1347861319320584 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hiroyasu Miyazaki Hiroyuki Watanabe Tetsuya Kitayama Masahiro Nishida Yasuhiro Nishi Koji Sekiya Hideki Suganami Keiji Yamamoto |
spellingShingle |
Hiroyasu Miyazaki Hiroyuki Watanabe Tetsuya Kitayama Masahiro Nishida Yasuhiro Nishi Koji Sekiya Hideki Suganami Keiji Yamamoto QT PRODACT: Sensitivity and Specificity of the Canine Telemetry Assay for Detecting Drug-Induced QT Interval Prolongation Journal of Pharmacological Sciences |
author_facet |
Hiroyasu Miyazaki Hiroyuki Watanabe Tetsuya Kitayama Masahiro Nishida Yasuhiro Nishi Koji Sekiya Hideki Suganami Keiji Yamamoto |
author_sort |
Hiroyasu Miyazaki |
title |
QT PRODACT: Sensitivity and Specificity of the Canine Telemetry Assay for Detecting Drug-Induced QT Interval Prolongation |
title_short |
QT PRODACT: Sensitivity and Specificity of the Canine Telemetry Assay for Detecting Drug-Induced QT Interval Prolongation |
title_full |
QT PRODACT: Sensitivity and Specificity of the Canine Telemetry Assay for Detecting Drug-Induced QT Interval Prolongation |
title_fullStr |
QT PRODACT: Sensitivity and Specificity of the Canine Telemetry Assay for Detecting Drug-Induced QT Interval Prolongation |
title_full_unstemmed |
QT PRODACT: Sensitivity and Specificity of the Canine Telemetry Assay for Detecting Drug-Induced QT Interval Prolongation |
title_sort |
qt prodact: sensitivity and specificity of the canine telemetry assay for detecting drug-induced qt interval prolongation |
publisher |
Elsevier |
series |
Journal of Pharmacological Sciences |
issn |
1347-8613 |
publishDate |
2005-01-01 |
description |
The purpose of this investigation was to define the sensitivity and specificity of the canine telemetry assay for detecting drug-induced QT interval prolongation. Data from twelve studies generated in the QT PRODACT project were used in this investigation. The study design was a 4 × 4 Latin square cross-over design and included the following drugs: MK-499, E-4031, terfenadine, haloperidol, cisapride, bepridil, propranolol, diphenhydramine, captopril, verapamil, amoxicillin, and ciprofloxacin. The estimated root squared error of the model, which estimated the slope of the QT-RR relationships for each animal, for all dogs during the pre-dosing period was 5.45%. Using the QT-RR model, the sensitivity and specificity in each cutoff value that judges QT prolongation were estimated based on the experiment errors and measurement errors in the 12 studies. When the cutoff value was 5%, the sensitivity in 10% prolongation was 0.978 and the specificity in 0% was 0.996. In conclusion, it was judged that a 5% cutoff value for changes in heart rate corrected QT interval using the canine telemetry assay is practical, and the sensitivity and specificity of the telemetry assay are very high when using the analytical method presented here. Based upon this information, the canine telemetry assay using the individual subject heart rate correction model is recommended as a sensitive test system for the in vivo assessment of risk for QT interval prolongation. Keywords:: dog, sensitivity, telemetry, QT, QTc |
url |
http://www.sciencedirect.com/science/article/pii/S1347861319320584 |
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